Cancer Research AMC Sign up for Cancer Research eTOC's
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ougolkov, A. V.
Right arrow Articles by Billadeau, D. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ougolkov, A. V.
Right arrow Articles by Billadeau, D. D.
[Cancer Research 65, 2076-2081, March 15, 2005]
© 2005 American Association for Cancer Research

Priority Reports

Glycogen Synthase Kinase-3ß Participates in Nuclear Factor {kappa}B–Mediated Gene Transcription and Cell Survival in Pancreatic Cancer Cells

Andrei V. Ougolkov1, Martin E. Fernandez-Zapico2, Doris N. Savoy1, Raul A. Urrutia2 and Daniel D. Billadeau1

1 Division of Oncology Research and 2 GI Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota

Requests for reprints: Daniel D. Billadeau, Mayo Clinic, Division of Oncology Research, 200 First Street Southwest, Rochester, MN 55905. Phone: 507-266-4334; Fax: 507-266-5146; E-mail: billadeau.daniel{at}mayo.edu.

Recent studies using glycogen synthase kinase-3ß (GSK-3ß)–deficient mouse embryonic fibroblasts suggest that GSK-3ß positively regulates nuclear factor {kappa}B (NF{kappa}B)–mediated gene transcription. Because NF{kappa}B is suggested to participate in cell proliferation and survival pathways in pancreatic cancer, we investigated the role of GSK-3ß in regulating these cellular processes. Herein, we show that pancreatic cancer cells contain a pool of active GSK-3ß and that pharmacologic inhibition of GSK-3 kinase activity using small molecule inhibitors or genetic depletion of GSK-3ß by RNA interference leads to decreased cancer cell proliferation and survival. Mechanistically, we show that GSK-3ß influences NF{kappa}B-mediated gene transcription at a point distal to the I{kappa} kinase complex, as only ectopic expression of the NF{kappa}B subunits p65/p50, but not an I{kappa} kinase ß constitutively active mutant, could rescue the decreased cellular proliferation and survival associated with GSK-3ß inhibition. Taken together, our results simultaneously identify a previously unrecognized role for GSK-3ß in cancer cell survival and proliferation and suggest GSK-3ß as a potential therapeutic target in the treatment of pancreatic cancer.

Key Words: GSK-3 • NF-{kappa}B




This article has been cited by other articles:


Home page
 Am. J. Physiol. Cell Physiol.Home page
W. Hu, F. Li, S. Mahavadi, and K. S. Murthy
Upregulation of RGS4 expression by IL-1{beta} in colonic smooth muscle is enhanced by ERK1/2 and p38 MAPK and inhibited by the PI3K/Akt/GSK3{beta} pathway
Am J Physiol Cell Physiol, June 1, 2009; 296(6): C1310 - C1320.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
S.-H. Wang, Y.-L. Shih, T.-C. Kuo, W.-C. Ko, and C.-M. Shih
Cadmium Toxicity toward Autophagy through ROS-Activated GSK-3{beta} in Mesangial Cells
Toxicol. Sci., March 1, 2009; 108(1): 124 - 131.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. Miyashita, K. Kawakami, M. Nakada, W. Mai, A. Shakoori, H. Fujisawa, Y. Hayashi, J.-i. Hamada, and T. Minamoto
Potential Therapeutic Effect of Glycogen Synthase Kinase 3{beta} Inhibition against Human Glioblastoma
Clin. Cancer Res., February 1, 2009; 15(3): 887 - 897.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
A. J. Galliher-Beckley, J. G. Williams, J. B. Collins, and J. A. Cidlowski
Glycogen Synthase Kinase 3{beta}-Mediated Serine Phosphorylation of the Human Glucocorticoid Receptor Redirects Gene Expression Profiles
Mol. Cell. Biol., December 15, 2008; 28(24): 7309 - 7322.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. V. Ougolkov, V. N. Bilim, and D. D. Billadeau
Regulation of Pancreatic Tumor Cell Proliferation and Chemoresistance by the Histone Methyltransferase Enhancer of Zeste Homologue 2
Clin. Cancer Res., November 1, 2008; 14(21): 6790 - 6796.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
W. Wilson III and A. S. Baldwin
Maintenance of Constitutive I{kappa}B Kinase Activity by Glycogen Synthase Kinase-3{alpha}/{beta} in Pancreatic Cancer
Cancer Res., October 1, 2008; 68(19): 8156 - 8163.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. Vene, P. Larghero, G. Arena, M. B. Sporn, A. Albini, and F. Tosetti
Glycogen Synthase Kinase 3{beta} Regulates Cell Death Induced by Synthetic Triterpenoids
Cancer Res., September 1, 2008; 68(17): 6987 - 6996.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Kotliarova, S. Pastorino, L. C. Kovell, Y. Kotliarov, H. Song, W. Zhang, R. Bailey, D. Maric, J. C. Zenklusen, J. Lee, et al.
Glycogen Synthase Kinase-3 Inhibition Induces Glioma Cell Death through c-MYC, Nuclear Factor-{kappa}B, and Glucose Regulation
Cancer Res., August 15, 2008; 68(16): 6643 - 6651.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Ma, J. Wang, Y. Gao, T.-W. Gao, G. Chen, K. A. Bower, M. Odetallah, M. Ding, Z. Ke, and J. Luo
The Role of Glycogen Synthase Kinase 3{beta} in the Transformation of Epidermal Cells
Cancer Res., August 15, 2007; 67(16): 7756 - 7764.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. V. Ougolkov, N. D. Bone, M. E. Fernandez-Zapico, N. E. Kay, and D. D. Billadeau
Inhibition of glycogen synthase kinase-3 activity leads to epigenetic silencing of nuclear factor {kappa}B target genes and induction of apoptosis in chronic lymphocytic leukemia B cells
Blood, July 15, 2007; 110(2): 735 - 742.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
Z. Nie, G. D. Bren, S. R. Vlahakis, A. A. Schimnich, J. M. Brenchley, S. A. Trushin, S. Warren, D. J. Schnepple, C. M. Kovacs, M. R. Loutfy, et al.
Human Immunodeficiency Virus Type 1 Protease Cleaves Procaspase 8 In Vivo
J. Virol., July 1, 2007; 81(13): 6947 - 6956.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
M. Kunnimalaiyaan, A. M. Vaccaro, M. A. Ndiaye, and H. Chen
Inactivation of glycogen synthase kinase-3{beta}, a downstream target of the raf-1 pathway, is associated with growth suppression in medullary thyroid cancer cells
Mol. Cancer Ther., March 1, 2007; 6(3): 1151 - 1158.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
E. Rodionova, M. Conzelmann, E. Maraskovsky, M. Hess, M. Kirsch, T. Giese, A. D. Ho, M. Zoller, P. Dreger, and T. Luft
GSK-3 mediates differentiation and activation of proinflammatory dendritic cells
Blood, February 15, 2007; 109(4): 1584 - 1592.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. V. Ougolkov, M. E. Fernandez-Zapico, V. N. Bilim, T. C. Smyrk, S. T. Chari, and D. D. Billadeau
Aberrant Nuclear Accumulation of Glycogen Synthase Kinase-3{beta} in Human Pancreatic Cancer: Association with Kinase Activity and Tumor Dedifferentiation
Clin. Cancer Res., September 1, 2006; 12(17): 5074 - 5081.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
X. Deng, D. Z. Ewton, S. Li, A. Naqvi, S. E. Mercer, S. Landas, and E. Friedman
The Kinase Mirk/Dyrk1B Mediates Cell Survival in Pancreatic Ductal Adenocarcinoma.
Cancer Res., April 15, 2006; 66(8): 4149 - 4158.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2005 by the American Association for Cancer Research.